Phage detection by a bacterial NLR-related protein is mediated by DnaJ

Aaron Whiteley — Tue, 04 Jun 2024 15:00:00 +0000

Phage detection by a bacterial NLR-related protein is mediated by DnaJ Aaron Whiteley Tue, 06/04/2024 - 09:00

Amy Conte , Madison Ruchel , Samantha Ridgeway , Emily Kibby , Toni Nagy , Aaron Whiteley

BioRxiv (2024). PubMed PMID: 38895412; PubMed Central PMCID: PMC11185742.

Abstract

Bacteria encode a wide range of antiphage systems and a subset of these proteins are homologous to components of the human innate immune system. Mammalian nucleotide-binding and leucine-rich repeat containing proteins (NLRs) and bacterial NLR-related proteins use a central NACHT domain to link detection of infection with initiation of an antimicrobial response. Bacterial NACHT proteins provide defense against both DNA and RNA phages. Here we determine the mechanism of RNA phage detection by the bacterial NLR-related protein bNACHT25 in E. coli. bNACHT25 was specifically activated by Emesvirus ssRNA phages and analysis of MS2 phage escaper mutants that evaded detection revealed a critical role for Coat Protein (CP). A genetic assay confirmed CP was sufficient to activate bNACHT25 but the two proteins did not directly interact. Instead, we found bNACHT25 requires the host chaperone DnaJ to detect CP. Our data suggest that bNACHT25 detects a wide range of phages by guarding a host cell process rather than binding a specific phage-derived molecule.

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Conte AN, Ridgeway SM, Ruchel ME, Kibby EM, Nagy TA, Whiteley AT. Phage detection by a bacterial NLR-related protein is mediated by DnaJ. bioRxiv. 2024 Jun 4;. doi: 10.1101/2024.06.04.597415. PubMed PMID: 38895412; PubMed Central PMCID: PMC11185742.

Conte AN, Ridgeway SM, Ruchel ME, Kibby EM, Nagy TA, ➤Whiteley, AT | BioRxiv 2024

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Phage detection by a bacterial NLR-related protein is mediated by DnaJ

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